Background:

Rapid increasing resistance in nosocomial pathogens has always been a challenge for clinicians and hospital infection control. Tigecycline, a member of a new class of antimicrobials (glycylcyclines), has been shown to have potent expanded broad spectrum activity against most species of Enterobacteriaceae as well as Gram positives, atypicals and anaerobes. The TEST program determined the in vitro activity of tigecycline compared to amikacin, ampicillin, imipenem, cefepime, ceftazidime, ceftriaxone, levofloxacin, minocycline and piperacillin/tazobactam against members of Enterobacteriaceae (mainly E. coli, Klebsiella spp., Enterobacter spp., and Serratia spp.) collected from hospitals in North America, Europe and Asia.

Methods:

A total of 3204 clinical isolates of Enterobacteriaceae were identified to the species level at each participating site and confirmed by the central laboratory. Isolates were collected throughout 2004. Minimum Inhibitory Concentration (MICs) were determined by the local laboratory using broth microdilution panels and interpreted according to NCCLS guidelines.

Results:

Tigecycline's activity was equivalent to imipenem presenting a MIC50/MIC90 of 0.25/1 mcg/mL against all strains of Enterobacteriaceae. In comparison to other antimicrobials tested, the MIC90 of 1 mcg/mL for tigecycline was also the lowest being 8 fold lower than commonly prescribed broad spectrum antimicrobials such as ceftriaxone, levofloxacin, and minocycline and 16 fold lower than ceftazidime and piperacillin/tazobactam. The frequency of ESBL production among K. pneumoniae and E. coli was found to be 10.3% and 2.2%, respectively. Tigecycline inhibited >98% of all E. coli and K. pneumoniae ESBL producers at an MIC of 2 mcg/mL. Approximately 20% of Enterobacter spp. and Serratia spp. presented resistance to third generation cephalosporins (ceftazidime and ceftriaxone) suggestive of AmpC-type resistance. Tigecycline also inhibited a majority of these isolates with an MIC90 of 2 mcg/mL.

Conclusion:

Tigecyclines in vitro activity was comparable to the activity of a broad spectrum antimicrobial, carbapenem (imipenem), and greater than other commonly prescribed broad spectrum agents tested in this study. The presented data suggest that tigecycline may be an effective therapeutic option against both susceptible strains of Enterobacteriaceae and multi-drug resistant strains regardless of degree or type of resistance.